1. Field of the Invention
The present invention relates to compounds comprising a potassium channel opener with superoxide ion (O2−) catalytic degradation properties and to pharmaceutical compositions comprising them. These compounds are useful for treatment, prevention and/or managing of diseases, disorders and conditions associated with oxidative stress or endothelial dysfunction.
2. Description of the Related Art
Openers of the mitochondrial ATP-regulated potassium channel have been shown to provide cytoprotection in experimental models of redox stress induced by ischemia-reperfusion or inflammation. However, the specificity for the mitochondrial rather than the sarcolemmal K+-ATP channel is important to eliminate the risk of systemic hypotension.
Given the demonstrated benefit in these pathological settings of therapeutic administration of either antioxidants or K+-ATP channel openers, a more substantial benefit may accrue from (i) the concomitant removal of reactive oxygen species (ROS) and (ii) stimulation of endogenous mechanisms (via opening K+-ATP channels) to protect against redox stress. This effect would be maximized if both these actions co-localized in space and time. However, such co-localization would be unlikely to occur by the co-administration of two distinct drugs, such as a separate K+-ATP channel opener and an anti-oxidant molecule, because of the unpredictability of their tissue distribution, metabolism, clearance, excretion, and intracellular localization.